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It had been believed that Crigler-Najjar syndrome type II (CN-II) is inherited as a recessive trait. I found a patient with CN-II, who had a heterozygous nonsense mutation on the gene for bilirubin UDP-glucuronosyltransferase (Br-UDPGT), indicating that CN-II is inherited both as a dominant and as a recessive trait. I speculated that the Br-UDPGT forms a tetramer on a lumen of endoplasmic reticulum. Because Peters et al. had reported that Br-UDPGT was composed of four subunits by radiation inactivation experiment. To elucidate the cause of the CN-II with a heterozygous nonsense mutation on a molecular level, I performed an SDS-PAGE, cross-linking experiment, protein-protein interaction experiment, and gel filtration column chromatography. Among thses experiments, I could clearly demonstrate the cause of the disease by protein-protein interaction experiment. At first, I constructed the plasmids of His-UGTCN-II and GST-UGTCN-II and overexpressed the His-UGTCN-II and GST-UGTCN-II fusion proteins. Then I performed Ni-affinity column chromatography. As expected, both fusion proteins were simultaniouly eluted with imidazol buffer, showing that the Br-UDPGT formed a complex. I could verify the CN-II is caused by a dominant negative mutation.